Benzene is an important industrial pollutant and a component of gasoline. Occupational exposures of this chemical also remain high in developing countries. Benzene is a known human leukemogen. Studies in animals and in exposed workers have shown that benzene is capable of producing various forms of chromosomal damage. One report suggests that this chromosomal damage may persist for a number of years and others suggest that the damage may be chromosome specific. Blood samples have been collected from two different cohorts and appropriate controls in Shanghai, China. The first cohort contains individuals with a past history of benzene poisoning and no current benzene exposure. The second cohort is currently exposed to levels of benzene between 10-25 ppm. The blood samples have been processed such that slides are available for the scoring of micronuclei, and chromosomal aberrations using fluorescence in situ hybridization (FISH). Buffy coats have also been prepared in which the level of benzene-related DNA adducts can be determined. We, therefore, propose to measure levels of micronuclei, aneuploidy and chromosomal translocations in slides prepared from these cohorts and appropriate controls. We also propose to prepare a benzene metabolite DNA adduct map and attempt to detect these DNA adducts in the white blood cells of the currently-exposed workers. The measurements will form part of a larger study in which other markers of susceptibility and damage, including the rate of P450 2E1 metabolism, will also be measured. The goals of the proposed work are, therefore, to: (1) validate three new biomarkers of genetic damage and internal dose in a field study; (2) compare the outcomes with other markers of dose effect and susceptibility; (3) determine the level and persistence of benzene- induced micronuclei and chromosome damage in peripheral blood cells; and (4) detect and identify the DNA adducts formed in peripheral blood cells following occupational exposure to benzene. These studies should greatly enhance our ability to characterize the risk posed by benzene exposure in humans.